血管紧张素转化酶抑制剂与血管紧张素受体拮抗剂临床疗效对比

肾素-血管紧张素-醛固酮系统（RAAS）激活与高血压及其他心血管不良事件密切相关。虽然血管紧张素转化酶抑制剂（ACEI）与血管紧张素受体拮抗剂（ARB）在高血压治疗中同样重要，但研究发现二者心血管系统保护作用差异明显。本文将综述评估上述药物临床疗效的相关研究。     

新型肾素抑制剂阿利吉仑临床应用的研究进展

许多心血管疾病和肾脏疾病的病理生理过程都伴有肾素-血管紧张素-醛固酮系统（RAAS）的激活。在高血压的治疗方案中,血管紧张素转化酶抑制剂（ACEIs）和血管紧张素受体阻滞剂（ARBs）成为一线用药。长期以来肾素被认为是RAAS中最经典、最合乎逻辑的药物靶标,然而,首个肾素抑制剂阿利吉仑在2007年才被批准用于高血压疾病的治疗。近年来阿利吉仑良好的血压控制效果及脏器保护效应备受关注。因阿利吉仑能更完全地抑制RAAS,以其为基础的联合用药方案对于预防高血压并发症业已取得良好效果。本文就近年来阿利吉仑在临床应用中的研究进展进行综述。     

ACEI和ARBs在糖尿病并发高血压中的应用

肾素血管紧张素醛固酮系统（RAAS）参与糖尿病及其血管并发症的整个过程，此外糖尿病、高血压、动脉粥样硬化又激活麟，形成一个血管紧张素Ⅱ（AngⅡ）的恶性循环。血管紧张素转化酶抑制剂（ACEⅠ）和血管紧张素Ⅱ受体阻断剂（ARBs）两类药物可以阻断RAAS，在治疗糖尿病合并高血压、肾病、冠脉疾病、心力衰竭等方面有薯舌垂告白作甩．     

为什么血管紧张素转化酶抑制剂能降低高血压患者死亡率?

最新荟萃分析发现,肾素-血管紧张素(Ang)-醛固酮系统(RAAS)抑制剂能降低高血压患者死亡率,其治疗获益全部源于血管紧张素转化酶(ACE)抑制剂(ACEIs),而非血管紧张素受体拮抗剂(ARBs)。RAAS可以归纳为2条轴:ACE-AngⅡ(1-8)-AT1受体轴和ACE2-Ang(1-7)-Mas受体轴,ACEIs对RAAS的2条轴均发挥良好作用,而ARBs主要作用于前者。各个指南推荐高血压相关心血管疾病治疗优先选择ACEIs,对不能够耐受者选择ARBs。我们应当重视ACEIs在高血压、冠心病、心肌梗死和心力衰竭防治中的应用,目的是降低心血管疾病患病率和死亡率的风险。     

血管紧张素受体拮抗剂抗房颤的作用——事实与争议

大量的基础研究证实,肾素-血管紧张素-醛固酮（RAAS）系统参与了促心律失常的病理生理过程。一些前瞻性临床试验也提示,使用血管紧张素受体拮抗剂（ARBs）阻断RAAS系统,在心房颤动（房颤）的一、二级预防中均能获益。近年来意大利多中心房颤试验（GISSI—AF）却报道了使用缬沙坦药物并不能预防房颤复发。该文对ARBs抗房颤的作用作一综述。     

血管紧张素受体拮抗剂抗房颤的作用——事实与争议

大量的基础研究证实,肾素-血管紧张素-醛固酮（RAAS）系统参与了促心律失常的病理生理过程。一些前瞻性临床试验也提示,使用血管紧张素受体拮抗剂（ARBs）阻断RAAS系统,在心房颤动（房颤）的一、二级预防中均能获益。近年来意大利多中心房颤试验（GISSI—AF）却报道了使用缬沙坦药物并不能预防房颤复发。该文对ARBs抗房颤的作用作一综述。     

血管紧张素受体阻滞剂在慢性心力衰竭治疗中的重要作用

肾素-血管紧张素-醛固酮系统（RAAS）在心血管疾病的发生、发展以及疾病的预后和并发症产生上均起着极其重要的作用。血管紧张素转换酶抑制剂（ACEI）作为一种阻断RAAS的药物,在心血管疾病的预防和治疗上功不可没。美国和中国的收缩期心力衰竭指南均将ACEI列为治疗的基石。但ACEI也有其缺陷或局限性：如对血管紧张素Ⅱ生成的阻遏作用是不完全的;对组织RAAS的阻遏作用可能并不理想,而组织RAAS对靶器官损害和预后有重要影响;长期使用会出现血管紧张素Ⅱ升高（逃逸现象）;临床上咳嗽的不良反应发生率较高,     

肾素-血管紧张素系统与心房颤动

研究表明,肾素-血管紧张素系统（RAS）激活在心房颤动（房颤）的发生和维持中发挥重要作用,应用血管紧张素转换酶抑制剂（ACEIs）和血管紧张素受体拮抗剂（ARBs）阻断RAS可逆转心房重构,从而预防房颤的发生。一些大规模随机对照临床试验（RCTs）的后续分析提示,ACEIs和ARBs可以减少心力衰竭和高血压忠者房颤的发生率。     

血管紧张素受体拮抗剂对高血压患者血管内皮的影响

血管内皮细胞（EC）具有调节血管紧张性及血压的作用。血管内皮功能异常主要表现为血管舒张因子及血管收缩因子之间浓度失衡,其中最具代表性的就是一氧化氮（NO）和血管紧张素Ⅱ。血管紧张素Ⅱ参与血压调节,还与动脉粥样硬化及心血管疾病危险性增加相关。高血压患者使用血管紧张素受体拮抗剂（ARBs）治疗,除了有降低血压作用外,其血管内皮功能也有明显改善。本文就血管紧张素受体拮抗剂对高血压患者血管内皮细胞功能的影响做一综述。     

反义基因疗法--治疗高血压病的新进展

肾素-血管紧张素-醛固酮系统（RAS）的过度活动是人类原发性高血压及许多高血压动物模型的主要病理机制之一。针对RAS的主要降压药物如血管紧张素转换酶抑制剂,血管紧张素Ⅱ受体Ⅰ拮抗剂虽然有良好的降压效果,但同时也有一些缺陷。针对RAS的反义基因疗法,在自发性高血压大鼠（SHR）等高血压动物模型身上已取得了明显而持久的降压作用,且能拮抗高血压引起的一系列病理生理改变,对靶器官有保护作用,成为新一代抗高血压药物的研究热点。本文将这一热点的研究进展做一综述。     

Angiotensin-II receptor blockers: benefits beyond blood pressure reduction?

Effective treatment of hypertension is essential to reduce the risk of renal and cardiovascular (CV) morbidity. The risks associated with hypertension are modulated by the presence of other factors. This has prompted the quest for agents that have benefits beyond blood pressure (BP) lowering. The angiotensin II receptor blocker (ARB) class of antihypertensive agents represents an important addition to the therapeutic options for elevated BP. Their ability to control BP is equivalent to existing therapies and there is a considerable and mounting evidence-base for their ability to reduce hypertension-associated target organ damage and comorbidities. Studies show that ARBs have clinical benefits across the spectrum of disease severity. In particular, recent large studies have demonstrated that these benefits extend to patients with conditions predisposing to CV events, such as diabetes, left ventricular hypertrophy and microalbuminuria, and where risk factors coexist. Data from these studies suggest that the CV protective effects of ARBs are at least, in part, independent from the BP lowering action. In addition, ARBs are extremely well tolerated, and strong evidence suggests that compliance with therapy--a key factor in achieving adequate BP control--with ARBs is higher than with other antihypertensive agents. Furthermore, flexible dosing and good tolerability profile mean that, where necessary, ARBs can be combined with other classes of antihypertensive agents to achieve adequate BP control and reduce the risk of hypertension-associated morbidity.     

Evaluation of the 24 h effects of the angiotensin II receptor blockers: means to improve cardiovascular outcomes?

Recent research has demonstrated that ambulatory BP is a superior means to predict cardiovascular outcomes in treated patients with hypertension. Ambulatory blood pressure monitoring has been utilized to evaluate the efficacy of all anti-hypertensive drugs including the angiotensin II receptor blockers (ARBs). This paper reviews the relationship of clinic and ambulatory blood pressures to cardiovascular outcomes and the benefits of ARBs to maximize improvement in clinical end-points in patients with hypertension. Clinical trial evidence has demonstrated that ARBs are a preferred class in patients with electrocardiographic evidence of left ventricular hypertrophy, in patients with type 2 diabetes, patients with chronic kidney disease, and in individuals with heart failure who have clinically relevant intolerability to angiotensin converting enzyme inhibitors. In addition, there is increasing evidence from clinical trials that many of the ARBs provide adequate 24 h blood pressure control alone or in combination with other anti-hypertensive agents. We conclude that the combination of event reduction from large-scale clinical trials, adequate 24 h BP reduction, and improved tolerability compared to most other classes of anti-hypertensive agents, make the ARBs a suitable initial treatment for patients with hypertension.     

Direkte Reninhemmer oder Kirene

Direct renin inhibitors (DRIs) are a new class of antihypertensive drugs. DRIs reduce the activity of the renin-angiotensin-aldosterone system (RAAS) and are therefore comparable to angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs). In contrast to the latter, however, they decrease the concentrations of all angiotensins and do not cause cough or angioedema. DRIs are highly specific and very well tolerated drugs. They are primarily used as antihypertensives, but promise to be useful for organ protection in other cardiovascular and renal diseases. DRIs are an alternative to other RAAS-blocking agents (ARBs, ACEIs, beta blockers, aldosterone antagonists), calcium channel blockers, and diuretics or can be used in combination with them. Aliskiren/Rasilez® is the first orally active DRI to provide long-acting antihypertensive effects and an excellent tolerability profile; it has been successfully used as a monotherapy and in combination with other antihypertensive drugs.     

Hypertension Management: Rationale for Triple Therapy Based on Mechanisms of Action

An estimated 25% of patients will require 3 antihypertensive agents to achieve blood pressure (BP) control; combination therapy is thus an important strategy in hypertension treatment. This review discusses the triple‐therapy combination of an angiotensin receptor blocker (ARB) or direct renin antagonist (DRI) with a calcium channel blocker (CCB) and a diuretic, with a focus on mechanisms of action. Multiple physiologic pathways contribute to hypertension. Combining antihypertensive agents not only better targets the underlying pathways, but also helps blunt compensatory responses that may be triggered by single‐agent therapy. DRIs and ARBs target the renin–angiotensin–aldosterone system (RAAS) at the initial and final steps, respectively, and both classes lower BP by reducing the effects of angiotensin‐2; however, ARBs may trigger a compensatory increase in renin activity. Dihydropyridine CCBs target L‐type calcium channels and lower BP through potent vasodilation, but can trigger compensatory activation of the sympathetic nervous system (SNS) and RAAS. Thiazide diuretics lower BP initially through sodium depletion and plasma volume reduction, followed by total peripheral resistance reduction, but can also trigger compensatory activation of the SNS and RAAS. The combination of an agent targeting the RAAS with a CCB and diuretic is rational, and triple combinations of valsartan/amlodipine/hydrochlorothiazide, olmesartan/amlodipine/hydrochlorothiazide, and aliskiren/amlodipine/hydrochlorothiazide have demonstrated greater effectiveness compared with their respective dual‐component combinations. In addition, single‐pill, fixed‐dose combinations can address barriers to BP control including clinical inertia and poor adherence. Fixed‐dose antihypertensive combination products capitalize on complementary mechanisms of action and have been shown to result in improved BP control.     

Cardiovascular consequences of poor compliance to antihypertensive therapy

Despite the proven efficacy of current strategies for cardiovascular (CV) risk reduction, a considerable gap remains between the risk reductions achieved in clinical trials and those seen in clinical practice. A major reason for this is poor compliance to medication, which has been extensively documented for antihypertensive therapy. Low adherence results in suboptimal blood pressure control, which is associated with adverse CV outcomes and increased treatment costs. Adverse effects of medication are an important cause of diminished adherence. Angiotensin II receptor blockers (ARBs) may offer better long-term tolerability than other classes of antihypertensive agent, and this is likely to be a major factor in the high levels of adherence and persistence seen with these agents. This could have implications for CV protection, as confirmed by the results of recent clinical trials. Thus, ARBs should be considered as an alternative to angiotensin-converting enzyme inhibitors in patients at risk of low adherence.     

Aliskiren in the treatment of hypertension and organ damage

Hypertension is one of the most important risk factor and cause of cardiovascular diseases (CVD). Chronic activation of the renin-angiotensin-aldosterone system (RAAS) plays a key role in the development of hypertension, cardiac and renal diseases. RAAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs), improve cardiovascular and renal outcomes. However, studies have shown that residual morbidity and mortality remains high, despite current optimal treatment. More comprehensive control of the RAAS might provide additional reductions in morbidity and mortality. Direct renin inhibitors such aliskiren offer the potential for enhanced RAAS control as they target the system at the point of activation, thereby reducing plasma renin activity; by contrast, ACEI and ARBs increase plasma renin activity. The efficacy of aliskiren in the reduction of major clinical events is being tested in large ongoing clinical trials. This review examines the efficacy, safety, and tolerability of aliskiren, and considers the evidence for the potential organ protection benefits of this treatment.     

Efficacy of Angiotensin Receptor Blockers in Cardiovascular Disease

The cardiovascular continuum describes the progression of pathophysiologic events from cardiovascular risk factors to symptomatic cardiovascular disease (CVD) and life-threatening events. Pharmacologic intervention early in the continuum may prevent or slow CVD development and improve quality of life. The renin–angiotensin–aldosterone system (RAAS) is central to the pathophysiology of CVD at many stages of the continuum. Numerous clinical trials of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have shown that RAAS blockade provides benefits to patients across the continuum. ARBs are as effective as ACE inhibitors in the treatment of hypertension; however tolerability and adherence to therapy appear to be improved with ARBs. Large clinical trials have shown that ARBs may provide therapeutic benefits beyond blood pressure control in patients with diabetes, heart failure or at risk of heart failure following a myocardial infarction. In addition, ARBs have been shown to provide protective effects in patients with impaired renal function or left ventricular hypertrophy. Additional clinical trials are ongoing to further characterize the role of ARBs in CVD management.     

Evidence for renoprotection by blockade of the renin-angiotensin-aldosterone system in hypertension and diabetes

The incidence of end-stage renal disease (ESRD) is rising worldwide, accompanied by corresponding increases in the risk of morbidity and mortality. Underlying this trend are increasing rates of hypertension and diabetes mellitus, the two most common causes of ESRD. In addition to the adverse haemodynamic effects of hypertension on the kidney, elevated blood pressure (BP) can activate components of the renin-angiotensin-aldosterone system (RAAS), which, in turn, activate mediators of inflammation, oxidative stress, cell growth, and matrix accumulation. Lowering BP reduces the risk of cardiovascular events and renal damage. Accumulating evidence from clinical and laboratory studies suggests that interrupting the RAAS with therapies such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and aldosterone receptor blockers can interfere with the mechanisms that promote diabetic and non-diabetic renal damage. Moreover, clinical trials of RAAS blockade have demonstrated reductions in microalbuminuria, a predictor of increased cardiorenal risk and overt nephropathy in patients with and without diabetes and/or hypertension. In this way, agents that block the RAAS should be considered the drugs of first choice as they provide enhanced renoprotection compared with other classes of antihypertensive agents such as calcium channel blockers and beta-blockers.     

Angiotensin receptor blockers: pharmacology, efficacy, and safety

J Clin Hypertens (Greenwich). 2011;13:677–686. ©2011 Wiley Periodicals, Inc.Key Points and Practical Recommendations

• • The angiotensin receptor blockers are highly effective antihypertensive agents that are also particularly well tolerated.
• • There are no major differences in efficacy or other clinical characteristics among older drugs in this class, although some of the newer agents may more effectively reduce blood pressure than older agents.
• • Major randomized clinical trials have demonstrated that angiotensin receptor blockers provide significant outcomes benefits in conditions such as diabetic nephropathy, chronic heart failure or heart failure following myocardial infarction, hypertension with left ventricular hypertrophy and in patients whose histories of previous events or complicated diabetes puts them at high cardiovascular risk.
• • In treating hypertension, angiotensin receptor blockers can be used as first‐line therapy or added at later stages of treatment titration.
• • These drugs are very effective in combination with thiazide diuretics or calcium channel blockers and there are several single‐pill, fixed‐dose combinations of angiotensin receptor blockers with hydrochlorothiazide, amlodipine, or aliskiren. These combinations can be given as initial therapy (where appropriate) or later in the course of treatment. Three‐drug combinations (angiotensin receptor blocker plus amlodipine plus hydrochlorothiazide and angiotensin receptor blocker plus aliskiren plus hydrochlorothiazide) are also available.

The renin‐angiotensin‐aldosterone system (RAAS) plays an important role in protecting vertebrates against cardiovascular collapse due to hypotension and volume loss in the event of traumatic injury that involves blood loss. In certain humans, however, inappropriate or exaggerated activity of the RAAS contributes to the development of hypertension and the initiation of a molecular cascade in tissues with consequent injury to critical organs such as the brain, kidneys, heart, and blood vessels. ¹ , ² , ³ As understanding of the pathologic role of the RAAS in hypertensive vascular disease has unfolded during the past century, so has the interest in developing drugs that could interdict specific components of the RAAS. The first of the RAAS‐blocking drugs to become commercially available were the aldosterone antagonists in the 1970s, followed by the angiotensin‐converting enzyme (ACE) inhibitors in the 1980s and the angiotensin II receptor blockers (ARBs) in the 1990s. Unlike ACE inhibitors that inhibit the conversion of angiotensin I to II, ARBs bind to the angiotensin II AT₁ receptor, thereby inhibiting the cellular actions of angiotension II mediated by the receptor in which the tissue is located. During the past 20 years, studies in the laboratory and clinic have documented that ARBs, either alone or in combination with drugs of other classes, reduce blood pressure (BP) in hypertensive animals and humans; reduce rates of myocardial infarction (MI), stroke, and progression of renal impairment; and positively impact other markers of cardiovascular (CV) events such as left ventricular hypertrophy (LVH) and urinary protein excretion independent of their effect on BP. Although improvement in mortality and morbidity has been demonstrated after treatment of patients with congestive heart failure (HF) and following MI, this review paper will focus primarily on evidence supporting the use of ARBs in the management of hypertensive patients with and without comorbidities.